Dual Functional Ultrasensitive Point-of-Care Clinical Diagnosis Using Metal-Organic Frameworks-Based Immunobeads.

Sepsis is an acute systemic infectious syndrome with high fatality. Fast and accurate diagnosis, monitoring, and medication of sepsis are essential. We exploited the fluorescent metal-AIEgen frameworks (MAFs) and demonstrated the dual functions of protein detection and bacteria identification: (i) ultrasensitive point-of-care (POC) detection of sepsis biomarkers (100 times enhanced sensitivity); (ii) rapid POC identification of Gram-negative/positive bacteria (selective aggregation within 20 min). Fluorescent lateral flow immunoassays (LFAs) are convenient and inexpensive for POC tests. MAFs possess a large surface area, excellent photostability, high quantum yield (∼80%), and multiple active sites serving as protein binding domains for ultrasensitive detection of sepsis biomarkers (IL-6/PCT) on LFAs. The limit of detection (LOD) for IL-6/PCT is 0.252/0.333 pg/mL. Rapid appraisal of infectious bacteria is vital to guide the use of medicines. The dual-functional fluorescent MAFs have great potential in POC tests for the clinical diagnosis of bacterial infections.

Dual Gold Nanoparticle/Chemiluminescent Immunoassay for Sensitive Detection of Multiple Analytes.

Multiple antibiotics and mycotoxins usually simultaneously exist in foods, which poses a serious threat to human health. How to detect them in one test with high sensitivity and fidelity is challenging. In this study, we develop a dual readout lateral flow immunodetection platform that can quantitatively detect five kinds of antibiotics and five kinds of mycotoxins within one sample. The platform is composed of a chip and a portable readout instrument where gold nanoparticle (AuNP)-based and chemiluminescence immunoassays could be performed to reach a maximum throughput of 220 analytes in one setting. For a rapid screen, qualitative analysis by detecting the color change of the deposited AuNPs on the chip could be realized. For quantitative results, chemiluminescence imaging and analysis can be completed within 15 min. Apart from the high throughput and high efficiency, this platform has a high detection sensitivity. For instance, the limit of detection (LOD) for thiamphenicol (a representative antibiotic) and fumonisins B1 (a representative mycotoxin) is 8 times and 40 times lower than those of the previously reported methods, respectively. Thus, this dual readout immunodetection platform is promising as a universal device for rapid and quantitative detection of multiple analytes with high throughput, high sensitivity, and high fidelity.

The Studies on Structure and Stability of CaBn Clusters.

Calcium-boron systems have excellent properties of hardness, strength, and chemical stability, and we studied a series of CaBn clusters to investigate their structures and relative stability. The results showed the most stable structures of CaBn clusters are not planar. The B atoms tend to get together and form the planar ring to stabilize the structure, and the Ca atoms are coordinated to the periphery of the formations. The average binding energy (Eb), fragmentation energy (EF), second-order energy difference (Δ2E), adiabatic detachment energy (ADE), and adiabatic electron affinity (AEA) of the CaBn clusters were calculated to investigate the relative stability and the ability of removing or obtaining an electron. As shown by the results, EF and Δ2E values had obvious odd-even alteration as n increased, which indicated that the formations CaB4, CaB6, and CaB8 were more stable. The ADE values for CaBn clusters with even values of n were higher than those with odd values of n, which indicated CaBn clusters with even values of n had difficultly removing an electron. The AEA values of CaB3 and CaB7 were larger than the others, which meant CaB3 and CaB7 easily obtained an electron. These results provide a useful reference for understanding the formation mechanism and stability of the alkaline earth metal boride as well as guidance for synthesizing the CaBn clusters.

Weakly ionized gold nanoparticles amplify immunoassays for ultrasensitive point-of-care sensors.

Gold nanoparticle-based lateral flow immunoassays (AuNP LFIAs) are widely used point-of-care (POC) sensors for in vitro diagnostics. However, the sensitivity limitation of conventional AuNP LFIAs impedes the detection of trace biomarkers. Several studies have explored the size and shape factors of AuNPs and derivative nanohybrids, showing limited improvements or enhanced sensitivity at the cost of convenience and affordability. Here, we investigated surface chemistry on the sensitivity of AuNP LFIAs. By modifying surface ligands, a surface chemistry strategy involving weakly ionized AuNPs enables ultrasensitive naked-eye LFIAs (~100-fold enhanced sensitivity). We demonstrated how this surface chemistry-amplified immunoassay approach modulates nanointerfacial bindings to promote antibody adsorption and higher activity of adsorbed antibodies. This surface chemistry design eliminates complex nanosynthesis, auxiliary devices, or additional reagents while efficiently improving sensitivity with advantages: simplified fabrication process, excellent reproducibility and reliability, and ultrasensitivity toward various biomarkers. The surface chemistry using weakly ionized AuNPs represents a versatile approach for sensitizing POC sensors.

Ultrasensitive point-of-care biochemical sensor based on metal-AIEgen frameworks.

Point-of-care (POC) biochemical sensors have found broad applications in areas ranging from clinical diagnosis to environmental monitoring. However, POC sensors often suffer from poor sensitivity. Here, we synthesized a metal-organic framework, where the ligand is the aggregation-induced emission luminogen (AIEgen), which we call metal-AIEgen frameworks (MAFs), for use in the ultrasensitive POC biochemical sensors. MAFs process a unique luminescent mechanism of structural rigidity-enhanced emission to achieve a high quantum yield (~99.9%). We optimized the MAFs to show 102- to 103-fold enhanced sensitivity for a hydrogel-based POC digital sensor and lateral flow immunoassays (LFIA). MAFs have a high affinity to directly absorb proteins, which can label antibodies for immunoassays. MAFs-based LFIA with enhanced sensitivity shows robust serum detection for POC clinical diagnosis.